META-ANALYSIS OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS: Causative Organisms and Possible Prevention

Pre-exposure prophylaxis (PrEP) for HIV prevention is a promising experimental approach currently being tested globally. A number of PrEP trials are evaluating the safety and effectiveness of PrEP in men who have sex with men (MSM) and other populations at risk for HIV, and results will be available from this first generation of efficacy trials over the next few years. Here we review the rationale for orally-administered antiretrovirals for prevention, and outline issues the first generation trials will address as well as questions that may be addressed in future studies. We also describe the rationale for combination prevention approaches that may combine PrEP with other prevention modalities as part of a larger prevention package.


INTRODUCTION AND OBJECTIVES:
The aim was to determine whether secondary prevention involving the comprehensive and intensive treatment of cardiovascular risk factors reduces cardiovascular events and cardiovascular mortality at 3-year follow up.

METHODS:
The study design comprised a randomized, controlled, open trial in a routine clinical practice setting. In total, 247 patients who presented with acute coronary syndrome or stroke were selected. They were randomized to comprehensive and intensive treatment of cardiovascular risk factors (n=121) or to follow-up based on usual care (n=126). The main study outcomes were the number of cardiovascular events and cardiovascular mortality at 3-year follow-up. The percentage of patients in whom each risk factor was successfully controlled was a secondary outcome.
RESULTS: Overall, 88.8% of patients assigned to the intensive treatment group had a low-density lipoprotein cholesterol level <100mg/dl compared with 56.4% of the usual-care group (relative risk [RR]=1.57; 95% confidence interval [CI], 1.28-1.93), and 75.7% of diabetics had a hemoglobin A(1c) <7% compared with 28.6% of the usual-care group (RR=2.65; 95% CI, 1. 13-6.19). There were four deaths due to cardiovascular causes and 26 nonfatal events in the intensive treatment group versus 17 deaths and 54 nonfatal events in the usual-care group. The cumulative survival rate at 3 years was 97.4% in the intervention group and 85.5% in the control group (p=.003).
CONCLUSIONS: Secondary prevention involving comprehensive and intensive treatment of cardiovascular risk factors reduced both morbidity and mortality at 3-year follow up.

Abstract
Postoperative atrial fibrillation and atrial flutter (POAF) are the most common complications of cardiac surgery that require intervention or prolong intensive care unit and total hospital stay. For some patients, these tachyarrhythmias have important consequences including patient discomfort/anxiety, hemodynamic deterioration, cognitive impairment, thromboembolic events including stroke, exposure to the risks of antiarrhythmic treatments, longer hospital stay, and increased health care costs. We conclude that prevention of POAF is a worthwhile exercise and recommend that the dominant therapy for this purpose be β-blocker therapy, especially the continuation of β-blocker therapy that is already in place. When βblocker therapy is contraindicated, amiodarone prophylaxis is recommended. If both of these therapies are contraindicated, therapy with either intravenous magnesium or biatrial pacing is suggested. Patients at high risk of POAF may be considered for first-line amiodarone therapy, first-line sotalol therapy, or combination prophylactic therapy. The treatment of POAF may follow either a rate-control approach (with the dominant therapy being β-blocking drugs) or a rhythm-control approach. Anticoagulation should be considered if persistent POAF lasts >72 hours and at the point of hospital discharge. The ongoing need for any POAF treatment (including anticoagulation) should be reconsidered 6-12 weeks after the surgical procedure.

Abstract
The stroke rate in atrial fibrillation is 4.5% per year, with death or permanent disability in over half. The risk of stroke varies from under 1% to over 20% per year, related to the risk factors of congestive heart failure, hypertension, age, diabetes, and prior stroke or transient ischemic attack (TIA). Major bleeding with vitamin K antagonists varies from about 1% to over 12% per year and is related to a number of risk factors. The CHADS(2) index and the HAS-BLED score are useful schemata for the prediction of stroke and bleeding risks. Vitamin K antagonists reduce the risk of stroke by 64%, aspirin reduces it by 19%, and vitamin K antagonists reduce the risk of stroke by 39% when directly compared with aspirin. Dabigatran is superior to warfarin for stroke prevention and causes no increase in major bleeding. We recommend that all patients with atrial fibrillation or atrial flutter, whether paroxysmal, persistent, or permanent, should be stratified for the risk of stroke and for the risk of bleeding and that most should receive antithrombotic therapy. We make detailed recommendations as to the preferred agents in various types of patients and for the management of antithrombotic therapies in the common clinical settings of cardioversion, concomitant coronary artery disease, surgical or diagnostic procedures with a risk of major bleeding, and the occurrence of stroke or major bleeding. Alternatives to antithrombotic therapies are briefly discussed.

Bischof Vukusic S, Flincec Grgac S, Budimir A, Kalenic S.
Sandra Bischof Vukusic, University of Zagreb, Faculty of Textile Technology, Prilaz baruna Filipovica 28a, 10 000 Zagreb, Croatia, sbischof@ttf.hr. Abstract Aim. To study the antimicrobial activity of citric acid (CA) and sodium hypophosphite monohydrate (SHP) against grampositive and gram-negative bacteria, and to determine the influence of conventional and microwave thermal treatments, on the effectiveness of antimicrobial treatment of cotton textiles. Method. Textile material was impregnated with CA and SHP solution and thermally treated by either conventional or microwave drying/curing treatment. Antibacterial effectiveness was tested according to ISO 20743:2009 standard, using absorption method. The surfaces were morphologically observed by scanning electron microscopy, while physical characteristics were determined by wrinkle recovery angles method (DIN 53 891), tensile strength (DIN 53 837), and whiteness degree method (AATCC 110-2000). Results. Cotton fabric treated with CA and SHP showed significant antibacterial activity against MRSA (6.38 log10 treated by conventional drying and 6.46 log10 treated by microwave drying before washing, and 6.90 log10 and 7.86 log10, respectively, after 1 cycle of home domestic laundering washing [HDLW]). Antibacterial activity was also remarkable against S. aureus (4.25 log10 by conventional drying, 4.58 log10 by microwave drying) and against P. aeruginosa (1.93 log10 by conventional drying and 4.66 log10 by microwave drying). Antibacterial activity against P. aeruginosa was higher in samples subjected to microwave than in conventional drying. Antibacterial activity was reduced after 10 HDLW cycles but the compound was still effective. The surface of the untreated cotton polymer was smooth, while minor erosion stripes appeared on the surfaces treated with antimicrobial agent, and long and deep stripes were found on the surface of the washed sample. Conclusion. CA can be used both for the disposable (non-durable) materials (gowns, masks, and cuffs for blood pressure measurement) and the materials that require durability to laundering. The current protocols and initiatives in infection control could be improved by the use of antimicrobial agents applied on cotton carbohydrate polymer.

Lin Y, Stanworth S, Birchall J, Doree C, Hyde C.
Abstract BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with haemophilia and inhibitory alloantibodies. It is also increasingly being used for off-license indications to prevent bleeding in operations where blood loss is likely to be high, and/or to stop bleeding that is proving difficult to control by other means.
OBJECTIVES: To assess the effectiveness of rFVIIa when used therapeutically to control active bleeding, or prophylactically to prevent (excessive) bleeding in patients without haemophilia.
SEARCH STRATEGY: We searched the Cochrane Injuries Group Specialised Register, CENTRAL, MEDLINE, EMBASE and other specialised databases up to 25 February 2009. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rFVIIa with placebo, or one dose of rFVIIa with another, in any patient population (except haemophilia). Outcomes were mortality, blood loss or control of bleeding, red cell transfusion requirements, number of patients transfused and thromboembolic adverse events.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed potentially relevant studies for inclusion, extracted data and examined risk of bias. We considered prophylactic and therapeutic rFVIIa studies separately.
MAIN RESULTS: Twenty-five RCTs were included: 24 were placebo-controlled double-blind RCTs and one compared different doses of rFVIIa.Fourteen trials involving 1137 participants examined the prophylactic use of rFVIIa; 713 received rFVIIa. There was no evidence of mortality benefit (RR 1.06; 95% CI 0.50 to 2.24). There was decreased blood loss (WMD -272 mL; 95% CI -399 to -146) and decreased red cell transfusion requirements (WMD -243 mL; 95% CI -393 to -92) with rFVIIa treatment; however these values were likely overestimated due to the inability to incorporate data from trials showing no difference of rFVIIa treatment compared to placebo. There was a trend in favour of rFVIIa in the number of participants transfused (RR 0.91; 95% CI 0.82 to 1.02). But there was a trend against rFVIIa with respect to thromboembolic adverse events (RR 1.32; 95% CI 0.84 to 2.06).Eleven trials involving 2366 participants examined the therapeutic use of rFVIIa; 1507 received rFVIIa. There were no outcomes where any observed advantage, or disadvantage, of rFVIIa over placebo could not have been observed by chance alone. There was a trend in favour of rFVIIa for reducing mortality (RR 0.89; 95% CI 0.77 to 1.03). However, there was a trend against rFVIIa for increased thromboembolic adverse events (RR 1.21; 95% CI 0.93 to 1.58).
AUTHORS' CONCLUSIONS: The effectiveness of rFVIIa as a more general haemostatic drug, either prophylactically or therapeutically, remains unproven. The use of rFVIIa outside its current licensed indications should be restricted to clinical trials.

Youssef MA, Al-Inany HG, Evers JL, Aboulghar M.
Abstract BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially fatal complication of ovarian stimulation, which affects 1% to 14% of all in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles. A number of clinical studies with conflicting results have reported on the use of intravenous fluids such as albumin, hydroxyethyl starch, Haemaccel® and dextran as a possible way for preventing the severe form of OHSS.
OBJECTIVES: To review the effectiveness and safety of administration of intravenous fluids such as albumin, hydroxyethyl starch, Haemaccel® and dextran in the prevention of severe ovarian hyperstimulation syndrome (OHSS) in IVF or ICSI treatment cycles.
SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, to third quarter 2010), MEDLINE (1950to November 2010, EMBASE (1980to November 2010 and The National Research Register (to November 2010). The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. The authors were contacted to provide or clarify data that were unclear from the trial reports.
SELECTION CRITERIA: Randomised controlled trials (RCTs) which compared the effects of intravenous fluids with placebo or no treatment for the prevention of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles.
DATA COLLECTION AND ANALYSIS: Two review authors independently scanned the abstracts, identified relevant papers, assessed inclusion of trials and trial quality and extracted relevant data. Validity was assessed in terms of method of randomisation, allocation concealment and outcomes. Where possible, data were pooled for analysis. A separate analysis of studies was performed for human albumin and hydroxyethyl starch versus placebo or no treatment. Other potential intravenous fluids have been identified, such as Haemaccel and dextran, however no randomised controlled studies on their applicability could be found.
MAIN RESULTS: Nine RCTs involving 1660 (human albumin vs placebo) and 487 (HES vs placebo) randomised women, have been included in this review. There was a borderline statistically significant decrease in the incidence of severe OHSS with administration of human albumin (8 RCTs, OR 0.67, 95% CI 0.45 to 0.99).There was a statistically significant decrease in severe OHSS incidence with administration of hydroxyethyl starch (3 RCTs, OR 0.12, 95% CI 0.04 to 0.40). There was no evidence of statistical difference in the pregnancy rate between both groups of treatment.
AUTHORS' CONCLUSIONS: There is limited evidence of benefit from intra-venous albumin administration at the time of oocyte retrieval in the prevention or reduction of the incidence of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles. Hydroxyethyl starch markedly decreases the incidence of severe OHSS.

Prevention of cerebral ischemia-induced memory deficits by inhibition of phosphodiesterase-4 in rats.
Li LX, Cheng YF, Lin HB, Wang C, Xu JP, Zhang HT.

Abstract
Inhibition of phosphodiesterase-4 (PDE4) by rolipram, a prototypical PDE4 inhibitor, reverses memory impairment produced pharmacologically or genetically. Comparably, much less is known about the effect of rolipram on cerebral ischemia-induced memory deficits. The objective of this study was to determine the effects of rolipram on ischemia-induced memory deficit, neuronal damage, and alteration of PDE4 activity in the hippocampus. Memory was examined using Morris water-maze and step-through passive avoidance tests in rats subjected to global cerebral ischemia with or without repeated treatment with rolipram (0.3 or 1 mg/kg, i.p.); neuronal damage in the hippocampus and PDE4 activity in hippocampal tissues were determined using Nissl staining and HPLC, respectively. In the water-maze test, cerebral ischemia significantly increased the escape latency to reach the platform during acquisition training and decreased the exploration time in the target quadrant in the probe trial test; these were blocked by rolipram in a dose-dependent manner. Rolipram also reduced the distracted platform searches induced by cerebral ischemia. In the passive avoidance test, ischemia decreased the 24-h latency to the dark compartment, which was also blocked by rolipram treatment. In addition, Nissl staining revealed ischemia-induced neuron loss in hippocampal CA1; this was blocked by rolipram. Further, cerebral ischemia led to increases in activity of PDE, primarily PDE4, in the hippocampus, which also was antagonized by rolipram. These results suggest that rolipram prevents cerebral ischemia-induced memory deficits via inhibition of increased PDE4 activity and attenuation of hippocampal, neuronal damages induced by ischemia. PDE4 may be a target for treatment of cognitive disorders associated with cerebral ischemia.
research related to tobacco product ingredients, nicotine, and harmful or potentially harmful constituents of tobacco products is discussed. DISCUSSION: Ingredients, which are additives, require less attention than nicotine and harmful or potentially harmful constituents. With respect to nicotine, the threshold level in tobacco products below which dependent users will be able to freely stop using the product if they choose to do so is a very important question. Harmful and potentially harmful constituents include various toxicants and carcinogens. An updated list of 72 carcinogens in cigarette smoke is presented. A crucial question is the appropriate levels of toxicants and carcinogens in tobacco products. The use of carcinogen and toxicant biomarkers to determine these levels is discussed. Conclusions: The need to establish regulatory standards for added ingredients, nicotine, and other tobacco and tobacco smoke constituents leads to many interesting and potentially highly significant research questions, which urgently need to be addressed. Lifestyle behaviors associated with secondary prevention of coronary heart disease among california adults.

Bellow A, Epstein JF, Parikh-Patel A.
Abstract INTRODUCTION: Heart disease is the leading cause of death in the United States. People diagnosed with coronary heart disease (CHD) are at an increased risk for illness and death. To reduce this risk, it is recommended that people who are diagnosed with CHD improve their health behaviors. The objective of this study was to assess the prevalence of associated lifestyle risk behaviors among California adults who have CHD.
METHODS: From 2005 through 2008, the California Behavioral Risk Factor Surveillance System collected data regarding previous diagnosis of cardiovascular diseases. We used these data to generate descriptive statistics to characterize the risk behaviors among people who had been diagnosed with CHD compared with people who had not, and developed multivariate logistic models to control for confounding variables.
RESULTS: Of total respondents, 5% reported previous diagnosis of CHD. Of respondents with CHD, three-quarters were not eating a healthful amount of fruits and vegetables, 66% were overweight or obese, 55% did not engage in regular physical activity, and nearly 15% were smokers. When we controlled for confounding variables, respondents who had been previously diagnosed with CHD were more likely than respondents who had not been diagnosed with CHD to be overweight or obese, to not exercise on a regular basis, and to be current smokers.
CONCLUSION: Adults in California with CHD are engaging in behaviors that put them at higher risk of illness and premature death. To lower death rates due to CHD, more public health efforts should target this population. Stroke Unit, Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy. Abstract The role of anticoagulants for the prevention of Background and Purpose: venous thromboembolism in acute hemorrhagic stroke is uncertain. We performed an updated meta-analysis of studies to obtain the best estimates of the efficacy and safety of anticoagulants for the prevention of venous thromboembolism in Using electronic and manual patients with acute hemorrhagic stroke. Methods: searches of the literature, we identified randomized and non randomized studies comparing anticoagulants (unfractionated heparin or low-molecular-weight heparin or heparinoids) with treatments other than anticoagulants (elastic stockings, intermittent pneumatic compression or placebo) in patients with acute hemorrhagic stroke. Study outcomes included symptomatic and asymptomatic deep venous thrombosis (DVT), symptomatic and asymptomatic pulmonary embolism (PE), any hematoma enlargement or death. Risk Ratio (RR) for individual outcomes were calculated for each study and data from all studies were pooled using the Four studies (2 randomized) involving 1000 Mantel-Haenszel method. Results: patients with acute hemorrhagic stroke met the criteria for inclusion in this meta-analysis. Compared with other treatments, anticoagulants were associated with a significant reduction in PE (1.7% versus 2.9%, RR 0.37, 95% CI: 0.17 to 0.80, p=0.01), a DVT rate of 4.2% compared to 3.3% (RR 0.77, 95% CI: 0.44 to 1.34, p=0.36), an increase in any hematoma enlargement (8.0% versus 4.0%, RR 1.42; 95% CI: 0.57 to 3.53, p=0.45), and a non significant reduction in mortality (16.1% versus 20.9%, RR 0.76; 95% CI: 0.57 to 1.03, p=0.07). Our findings indicate that in patients with hemorrhagic stroke, Conclusions: early anticoagulation is associated with a significant reduction in PE, a non significant reduction in mortality, with the trade-off of a non significant increase in hematoma enlargement. These results must be taken with caution and should encourage the assessment of the clinical benefit of antithrombotic prophylaxis in patients with cerebral bleeding by properly designed clinical trials. being revealed during a national health reform debate, have even been perceived as "rationing care." Others see them as "rational care," because they encourage utilization of beneficial services while discouraging use of those that may lead to more harms than benefits. Development of prevention guidelines requires value judgments, so despite the use of evidence, these recommendations have not all achieved widespread support. Understanding the data behind the guidelines, health care providers can decide how to approach prevention in practice, taking into consideration individual patient risk factors and preferences. Complementary and alternative medicine for prevention and treatment of the common cold.

Nahas R, Balla A.
Seekers Centre for Integrative Medicine, Ottawa, ON. richard@seekerscentre.com Abstract OBJECTIVE: To review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults.
QUALITY OF EVIDENCE: MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies were included.
MAIN MESSAGE: For prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold.
CONCLUSION: Vitamin C can be recommended to Canadian patients for prevention of the common cold. There is moderate evidence supporting the use of Echinacea purpurea and zinc lozenges for treatment. Ginseng and allicin warrant further research.

Abstract
To define whether hyperoxia induces the dysfunction of membrane fusion between synaptic vesicles with pre-synaptic plasma membranes in the nerve terminals, and whether vitamin E prevents this abnormal event, we investigated the influence of hyperoxia on the fusion ability of isolated synaptic vesicles and the inside-out type pre-synaptic plasma membrane vesicles from rat brain using the fluorescence tracing method. The membrane fusion ability of both membranes from rats subjected to hyperoxia was markedly decreased compared with the membranes from a normal rat. Rats subjected to hyperoxia in the form of oxidative stress showed significant increases in the levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes, and protein carbonyl moieties in both synaptic vesicles and pre-synaptic plasma membranes. When rats were supplemented with vitamin E, these abnormalities were inhibited even when rats were subjected to hyperoxia.

Abstract
Streptococcus pneumoniae is a leading cause of mortality in young children. While successful conjugate polysaccharide vaccines exist, a less expensive serotype-independent protein-based pneumococcal vaccine offers a major advancement for preventing life-threatening pneumococcal infections, particularly in developing nations. IL-17A-secreting CD4+ T cells (T(H)17) mediate resistance to mucosal colonization by multiple pathogens including S. pneumoniae. Screening an expression library containing >96% of predicted pneumococcal proteins, we identified antigens recognized by T(H)17 cells from mice immune to pneumococcal colonization. The identified antigens also elicited IL-17A secretion from colonized mouse splenocytes and human PBMCs suggesting that similar responses are primed during natural exposure. Immunization of two mouse strains with identified antigens provided protection from pneumococcal colonization that was significantly diminished in animals treated with blocking CD4 or IL-17A antibodies. This work demonstrates the potential of proteomic screening approaches to identify specific antigens for the design of subunit vaccines against mucosal pathogens via harnessingT(H)17mediated immunity.

Treatment and prevention of cryptosporidiosis: what options are there for a country like Zambia?
Kelly P.

Abstract
SUMMARYCryptosporidiosis is a major infection of humans, leading to diarrhoea and growth failure in children, diarrhoea and malnutrition in immunocompromised adults, and is associated with increased mortality in all age groups. Using the country of Zambia as an example, I review the possible approaches to treatment and prevention in a tropical setting. The current optimal therapy for cryptosporidiosis is nitazoxanide which works well in HIV uninfected children, but treatment in patients with HIV infection remains remarkably difficult. No single drug has demonstrated efficacy in a randomised trial. No vaccine is available, so the best option for prevention for the moment is filtration and clean storage of drinking water. This would be expected to reduce cryptosporidiosis dramatically, but this needs to be demonstrated directly. Water filtration would have the added benefit of protection against many other pathogens, but the paucity of alternative approaches highlights the need for a better understanding of this important human pathogen

25-Eur Spine J. 2011 Feb 15. [Epub ahead of print]
Evaluation of tenoxicam on prevention of arachnoiditis in rat laminectomy model.

Abstract
Post laminectomy arachnoiditis has been shown by experiments with rats and post operative radiological imaging in humans. The purpose of this experimental study was to determine the efficacy of tenoxicam in preventing arachnoiditis in rats. Twenty-four Wistar rats were divided into two groups, and L3 laminectomy was performed. In the tenoxicam group, 0.5 mg/kg tenoxicam was applied intraperitoneally. Normal saline was applied intraperitoneally in the control group. Later, the rats were killed at weeks 3 and 6, and the laminectomy sites were evaluated pathologically for arachnoiditis. The results showed that 6 weeks after surgery, the tenoxicam group showed lowest arachnoiditis grades. However, statistically significant difference was not found in arachnoiditis between the control group and the tenoxicam group. Based on these findings it is concluded that application of the tenoxicam after lumbar laminectomy did not effectively reduce arachnoiditis. Performing the most effective surgical technique without damage around tissue in a small surgical wound and having meticulous hemostasis in surgery seem to be the key for preventing arachnoiditis effectively.